Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, PR China.
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection and Shenzhen Agricultural Genome Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China.
Carbohydr Res. 2022 Oct;520:108629. doi: 10.1016/j.carres.2022.108629. Epub 2022 Jul 6.
The inhibition of function-specific β-N-acetyl-D-hexosaminidases, such as OfHex1 from the Asian corn borer (Ostrinia furnacalis), is a promising strategy for the development of green pesticides. Among reported OfHex1 inhibitors, glycosyl inhibitors show especially high inhibitory activity. In this study, a series of novel C-glycosidic oximino carbamate derivatives were designed using the OfHex1 crystal structure and synthesized. Among the C-Glycoside derivatives studied, compound 7k exhibited the best inhibitory activity against OfHex1 (IC = 47.47 μM). Compound 7k also exhibited excellent larvicidal activity against Plutella xylostella. The potential inhibitory mechanism of 7k was studied using molecular docking. Notably, compound 7k is the first reported C-glycoside inhibitor of OfHex1. These results provide direction for the rational design of novel OfHex1 inhibitors.
功能特异性β-N-乙酰-D-氨基己糖苷酶的抑制作用，如亚洲玉米螟（Ostrinia furnacalis）的OfHex1，是开发绿色农药的有前途的策略。在报道的OfHex1 抑制剂中，糖基抑制剂显示出特别高的抑制活性。在这项研究中，使用 OfHex1 晶体结构设计并合成了一系列新型 C-糖苷肟基氨基甲酸酯衍生物。在所研究的 C-糖苷衍生物中，化合物 7k 对 OfHex1 表现出最好的抑制活性（IC = 47.47 μM）。化合物 7k 对小菜蛾也表现出优异的杀虫活性。使用分子对接研究了 7k 的潜在抑制机制。值得注意的是，化合物 7k 是第一个报道的 OfHex1 的 C-糖苷抑制剂。这些结果为新型 OfHex1 抑制剂的合理设计提供了方向。
